Spatiotemporal Delivery of pBMP2 and pVEGF by a Core-Sheath Structured Fiber-Hydrogel Gene-Activated Matrix Loaded with Peptide-Modified Nanoparticles for Critical-Sized Bone Defect Repair

He, Shan1,2; Fang, Ju1; Zhong, Chuanxin1; Wang, Min2; Ren, Fuzeng1

2022-08-01

10.1002/adhm.202201096

Advanced Healthcare Materials   Impact Factor & Quartile

2192-2640

2192-2659

The clinical translation of bioactive scaffolds for the treatment of large segmental bone defects remains a grand challenge. The gene-activated matrix (GAM) combining gene therapy and tissue engineering scaffold offers a promising strategy for the restoration of structure and function of damaged or dysfunctional tissues. Herein, a gene-activated biomimetic composite scaffold consisting of an electrospun poly(epsilon-caprolactone) fiber sheath and an alginate hydrogel core which carried plasmid DNA encoding bone morphogenetic protein 2 (pBMP2) and vascular endothelial growth factor (pVEGF), respectively, is developed. A peptide-modified polymeric nanocarrier with low cytotoxicity and high efficiency serves as the nonviral DNA delivery vector. The obtained GAM allows spatiotemporal release of pVEGF and pBMP2 and promotes osteogenic differentiation of preosteoblasts in vitro. In vivo evaluation using a critical-sized segmental femoral defect model in rats shows that the dual gene delivery system can significantly accelerate bone healing by activating angiogenesis and osteogenesis. These findings demonstrate the effectiveness of the developed dual gene-activated core-sheath structured fiber-hydrogel composite scaffold for critical-sized bone defect regeneration and the potential of cell-free scaffold-based gene therapy for tissue engineering.

bone regeneration composite scaffolds gene delivery gene-activated matrix spatiotemporal

SCI ; EI

English

First ; Corresponding

National Key Research and Development Program of China[2016YFB0700803] ; Fundamental Research Program of Shenzhen, China[JCYJ20170307110418960]

Engineering ; Science & Technology - Other Topics ; Materials Science

Engineering, Biomedical ; Nanoscience & Nanotechnology ; Materials Science, Biomaterials

WOS:000846477600001

WILEY

20223512674397

Biomimetics ; Bone ; Cell engineering ; Defects ; Gene therapy ; Gene transfer ; Hydrogels ; Scaffolds (biology) ; Tissue regeneration

Biomedical Engineering:461.1 ; Biological Materials and Tissue Engineering:461.2 ; Biotechnology:461.8 ; Genetic Engineering:461.8.1 ; Biology:461.9 ; Colloid Chemistry:801.3 ; Chemical Products Generally:804 ; Materials Science:951

Web of Science

1.Southern Univ Sci & Technol, Dept Mat Sci & Engn, Shenzhen 518055, Guangdong, Peoples R China
2.Univ Hong Kong, Dept Mech Engn, Pokfulam Rd, Hong Kong 999077, Peoples R China

He, Shan,Fang, Ju,Zhong, Chuanxin,et al. Spatiotemporal Delivery of pBMP2 and pVEGF by a Core-Sheath Structured Fiber-Hydrogel Gene-Activated Matrix Loaded with Peptide-Modified Nanoparticles for Critical-Sized Bone Defect Repair[J]. Advanced Healthcare Materials,2022.

He, Shan,Fang, Ju,Zhong, Chuanxin,Wang, Min,&Ren, Fuzeng.(2022).Spatiotemporal Delivery of pBMP2 and pVEGF by a Core-Sheath Structured Fiber-Hydrogel Gene-Activated Matrix Loaded with Peptide-Modified Nanoparticles for Critical-Sized Bone Defect Repair.Advanced Healthcare Materials.

He, Shan,et al."Spatiotemporal Delivery of pBMP2 and pVEGF by a Core-Sheath Structured Fiber-Hydrogel Gene-Activated Matrix Loaded with Peptide-Modified Nanoparticles for Critical-Sized Bone Defect Repair".Advanced Healthcare Materials (2022).